Biomarker May Predict Adverse Events in Afib

Action Points

In this large cohort study, plasma von Willebrand Factor levels were independently assocaited with adverse events, including stroke, mortality, and major bleeding in anticoagulated atrial fibrillation patients.

Note, too, that further research is required to replicate these findings in a prospective, randomized trial and the prognostic utility of vWF in patients on other anticoagulants should be investigated.

Elevated plasma levels of a marker of endothelial damage may be a risk factor for adverse cardiovascular events in anticoagulated patients with permanent atrial fibrillation, researchers found.

High levels of von Willebrand factor were associated with greater risks of all-cause mortality, major bleeding, and a composite of cardiovascular outcomes (P<0.05 for all), according to Gregory Lip, MD, of the University of Birmingham Center for Cardiovascular Sciences in Birmingham, England, and colleagues.

The strongest association was with stroke (HR 5.04, 95% CI 2.40 to 10.59), the researchers reported online in the Journal of the American College of Cardiology.

"This biomarker may potentially be used to refine stroke and bleeding clinical risk stratification in atrial fibrillation," they wrote.

"It is ... uncertain whether plasma von Willebrand factor levels bring a new, different physiological factor into stroke prediction in atrial fibrillation patients or simply a measure of severity of previously identified clinical predictors," they added, noting that the relationships remained significant after adjusting for several risk factors for thrombotic and hemorrhagic events.

Lip and his colleagues evaluated the prognostic value of plasma levels of von Willebrand factor and fibrin D-dimer -- a marker of fibrin turnover and thrombogenesis -- in 829 patients (median age 76) who had permanent atrial fibrillation and were stabilized for at least six months on oral anticoagulants.

During a follow-up of more than two years (median 828 days), 95 patients had an adverse cardiovascular event -- a rate of 5% per year.

There were 69 deaths -- of which 25 were due to cardiovascular causes -- and 68 major bleeding episodes.

Plasma levels of fibrin D-dimer were not associated with adverse cardiovascular events, mortality, or bleeding.

In a multivariate analysis, however, elevated plasma von Willebrand factor levels (221 IU/dL and higher) were associated with adverse cardiovascular events (HR 2.79), along with an age of 75 or older (HR 2.00), history of stroke (HR 1.81), and history of heart failure (HR 1.79), significant at P<0.05 for all.

High plasma levels of von Willebrand factor were also associated with all-cause mortality and major bleeding (HRs 2.03 and 4.47, respectively, P<0.05 for both).

The researchers found that when plasma von Willebrand factor levels were added to two clinical risk stratification models for stroke -- CHADS2 and CHA2DS2-VASc -- and one for bleeding -- HAS-BLED -- the marker added prognostic value.

In an accompanying editorial, Victor Serebruany, MD, PhD, of Johns Hopkins University's HeartDrug Research Laboratories in Towson, Md., said that plasma von Willebrand factor levels may enhance risk stratification in patients with atrial fibrillation, but that more work needs to be done.

"First, serial assessment of von Willebrand factor in atrial fibrillation patients is urgently needed to better validate this promising biomarker, linking its immediate changes to the timing of adverse events," he wrote.

"Second, it is unclear to what degree the choice of an antithrombotic will affect the ability of soluble von Willebrand factor to predict prognosis," he continued. "This is especially true because warfarin is currently being aggressively substituted with novel thrombin inhibitors."

"Finally," he wrote, "these intriguing data need to be confirmed in a properly designed and adequately powered randomized trial."

The study authors acknowledged that the study was limited by the lack of information on the patients' time in the therapeutic range (INR 2.0 to 3.0) during follow-up.

The study was partially supported by grants from the Instituto de Salud Carlos III.

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